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Effects of cohort, genotype, variant, and maternal β-blocker treatment on foetal heart rate predictors of inherited long QT syndrome
Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Anschutz Medical Campus, CO, Aurora, United States.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Department of Physiology, University of Auckland, Auckland, New Zealand.ORCID-id: 0000-0002-9323-3166
Department of Pediatric Cardiology, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, Netherlands; Department of Cardiology, University Medical Center, Amsterdam, Netherlands.
Department of Pediatrics, Division of Cardiology, University of Utah School of Medicine, UT, Salt Lake City, United States.
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2023 (Engelska)Ingår i: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 25, nr 11, artikel-id euad319Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

AIMS: In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal β-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS.

METHODS AND RESULTS: In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal β-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7-42 weeks' GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or β-adrenergic response) had lower FHR. Maternal β-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity.

CONCLUSION: Genotype, LQT1 variant, and maternal β-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant's a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.

Ort, förlag, år, upplaga, sidor
Oxford University Press, 2023. Vol. 25, nr 11, artikel-id euad319
Nyckelord [en]
Bradycardia, Channelopathy, Foetal arrhythmia, Foetus, Inherited arrhythmias, Long QT syndrome, Potassium currents, Stillbirth, Sudden death
Nationell ämneskategori
Reproduktionsmedicin och gynekologi Kardiologi
Identifikatorer
URN: urn:nbn:se:umu:diva-217540DOI: 10.1093/europace/euad319ISI: 001107634900003PubMedID: 37975542Scopus ID: 2-s2.0-85177987474OAI: oai:DiVA.org:umu-217540DiVA, id: diva2:1819309
Tillgänglig från: 2023-12-13 Skapad: 2023-12-13 Senast uppdaterad: 2023-12-15Bibliografiskt granskad

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Winbo, AnnikaRydberg, Annika

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